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本研究建立并验证了一种灵敏、快速、简单的液质联用方法,用于同时测定BABL/c裸鼠血浆中舒尼替尼及其活性代谢产物SU12662的药物浓度。血浆样品采用蛋白沉淀方法处理,并使用帕唑帕尼作为内标。采用C18反相柱进行分离,流动相为10 mM甲酸胺–乙腈(65:35,v/v,pH 3.25),流速0.5 m L/min。所有化合物均采用电喷雾电离源,正离子方式检测。舒尼替尼及SU12662的最低定量下限均为0.5 ng/m L,线性范围均为0.5–1000 ng/m L(r>0.99)。该方法对舒尼替尼及SU12662的测定均具有良好准确度以及可靠的日内、日间精密度,方法稳定性良好,无明显基质效应。此方法成功用于BABL/c裸鼠口服20 mg/kg舒尼替尼的药物代谢动力学研究。
This study established and validated a sensitive, rapid and simple LC-MS method for the simultaneous determination of sunitinib and its active metabolite SU12662 in plasma of BABL / c nude mice. Plasma samples were treated by protein precipitation and pazopanib was used as an internal standard. The separation was performed on a C18 reverse phase column with a mobile phase of 10 mM formamide-acetonitrile (65:35, v / v, pH 3.25) at a flow rate of 0.5 mL / min. All compounds are electrospray ionization source, positive ion detection. The lowest limit of quantitation for sunitinib and SU12662 was 0.5 ng / mL, with a linear range of 0.5-1000 ng / mL (r> 0.99). The method for the determination of sunitinib and SU12662 have good accuracy and reliable intra-day and inter-day precision, good stability of the method, no obvious matrix effect. This method was successfully used to study the pharmacokinetics of sunitinib at a dose of 20 mg / kg in BABL / c nude mice.